Project Summary/Abstract Human health is highly dependent upon proper gene expression. Understanding how genes are regulated is critical in our understanding how mis- regulation leads to diseases. One major point where genes are regulated is during the assembly of the transcription machinery. This project is focused on understanding the molecular events that govern the assembly of the transcription machinery at promoters. The model system is the budding yeast Saccharomyces cerevisiae, because of its experimental tractability and the mechanistic similarities to assembly of the transcription machinery in humans. The project will assess the extent to which individual transcription regulators are dependent upon other transcriptional regulator for binding to the promoters of all Saccharomyces genes upon induction by heat shock. The project will examine in greater mechanistic details portions of the assembly process that involve the transcription pre-initiation complex. In particular, the interplay between chromatin and two major TBP delivery complexes (TFIID and SAGA) will be investigated. We will apply what we have learned from yeast to ask related but highly directed questions at multi-cellular model systems, with particular emphasis on human cells.